The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

Monday, April 18, 2016

Nivolumab Shows Impressive OS in melanoma

Single-agent
nivolumab (Opdivo) demonstrated a robust 5-year overall survival (OS) rate of
34% for heavily pretreated patients with metastatic melanoma who had not
received prior ipilimumab (Yervoy), according to long-term findings from a
single-arm phase I study presented at the 2016 AACR Annual Meeting.

Findings from the study, which began enrolling patients in 2008, represent the
first report of long-term outcomes from a clinical trial exploring a PD-1
inhibitor. In the study, the 5-year survival rate with nivolumab was double
survival statistics from the SEER database. From 2006 to 2012, the database
lists a 5-year survival rate of 17.9%.

“These data represent the longest survival follow-up of patients who received
anti–PD-1 therapy in a clinical study, and suggest durable, long-term survival
with nivolumab monotherapy,” said lead investigator F. Stephen Hodi, MD,
director of the Melanoma Center at Dana-Farber Cancer Institute. “Nivolumab
continued to be safe and tolerable, with no deaths or new safety signals”

In the study, which was labeled CA209-003, 107 patients received nivolumab
across 5 dose levels every 2 weeks. Doses were escalated from 0.1 mg/kg to 10
mg/kg and were continued for greater or equal to 96 weeks. The primary
endpoints were safety and tolerability with secondary outcomes focused on
efficacy, with an amendment to the original protocol to assess long-term OS.

The median age of patients was 61 years, and most had an ECOG PS of 0 or 1
(97%). Sixty-two percent of patients had received ≥2 prior therapies, including
46% who received prior interleukin-2. Overall, 78% of patients had visceral
metastases at baseline and 36% had elevated LDH levels.

After a minimum follow-up of 45 months, median OS was 17.3 months (95% CI,
12.5-37.8). According to the Kaplan-Meier curves, the median survival plateaued
at month 48, with a follow-up duration of 80 months for some patients. At 30
months, the progression-free survival (PFS) rate was 18.6%.

In those treated specifically with the 3-mg/kg dose of nivolumab (n = 17), which
is the FDA-approved dose, the median OS was 20.3 months (95% CI, 7.2-NR). The
5-year OS rate was 35.3% and the 30-month PFS rate was 25.7%.

“In all patients, there is a plateauing, a so called tail on the curve, and
it’s lasting many months to years, and about a third of patients have this
long-term survival,” said Hodi. “Those who make it to 48 months, have a very
good chance of surviving their disease.”

An exploratory analysis looked at patients who were retreated with single-agent
nivolumab. Patients were eligible for retreatment if they had initial disease
control and subsequent progression, no dose-limiting adverse events (AEs), and
went 1 year without progressive disease. Patients restarted nivolumab at the
same dose originally assigned for up to a total of 3 years including the
initial treatment period.

Five patients who were off treatment for 100 days experienced durable disease
control with nivolumab retreatment. One patient in this group, who remains on
treatment, had adrenal metastasis that was excised, resulting in no evidence of
disease and a long-term benefit.

“Updated analysis of retreated patients showed that disease control was
maintained,” said Hodi. “This demonstrates the importance of the durability of
clinical benefit for patients; now, we are measuring in terms years. As well as
the memory aspect, how the immunologic memory translated to better outcomes.”

Across all dose levels, 84.1% of patients experienced an AE, with 23.4% being
grade 3/4 in severity. At 3 mg/kg, all-grade AEs were 88.2% and grade 3/4 AEs
occurred in 35.3% of patients.

The most common nivolumab-related all-grade AEs across doses were fatigue
(29.9%), rash (23.4%), diarrhea (17.8%), pruritus (13.1%), and nausea (8.4%).
AEs led to treatment discontinuation for 10.3% of patients. The most common
grade 3/4 AEs were lymphopenia (2.8%), fatigue (1.9%), diarrhea (1.9%), and
nausea (0.9%).

Initial findings from the phase I study, which also enrolled patients with
renal cell carcinoma (RCC) and non–small cell lung cancer (NSCLC), ushered in a
new era focused on immunotherapy. Following a presentation of the results at
the 2012 ASCO Annual Meeting, a number of larger studies were initiated, which
quickly led to approvals for nivolumab across a variety of settings based on
phase III studies.

“What distinguishes immunotherapy from other forms of cancer treatment is the
durability of the benefit. Those who have complete responses seem to be
protected from that disease recurring,” said Louis M. Weiner, MD, director of
the Georgetown Lombardi Comprehensive Cancer Center, who moderated a press
conference. “The memory and the adaptability of the immune response to pick off
resistant variables is an important take-home here. These are very compelling
data to suggest that this is the case.”

Nivolumab is currently approved as a single-agent and in combination with
ipilimumab for patients with metastatic melanoma. Additionally, the agent is
approved for patients with non-squamous and squamous NSCLC and for those with
metastatic RCC.

An application to further expand nivolumab's indication is currently pending
with the FDA, for use of the PD-1 inhibitor to treat patients with classical
Hodgkin lymphoma, with a decision expected in the second half of 2016.
Additionally, an application will be filed within the coming months for the
agent as a treatment for head and neck cancer, based on an extension in OS in a
phase III study.

My last dose of nivo was in June of 2013. This study was pre-me and my ratties. And....you have to remember that my ratties and I were in an NED arm vs an active disease arm...all of us immunotherapy naive, in an escalating dose plan with the first 10 of us getting 1mg/kg (this was my group), the next getting 3mg/kg, and the last additional 10 getting 10mg/kg. Many, many arms were added later...but this is how we began...and we're hang'n in there pretty well. Way to go ratties!!! - c

PS.... this was in my lunch today...."I be ride'n the tail!" Yes, my lunch is packed daily...not by me. Has been. Always. Even when I worked night shift. I arrived at work with grocery bags full of pop tarts, sandwiches, Dinty Moore canned stew...with the label crossed out with "Les is Moore" hand written in. Yes, I ate it all. It kept me awake and therefore, my patients alive. And the lunches always...always...included a note. Of course my nurses, who now snatch up the note even before I see it, thought today's note salacious. At first....I was just confused. But then....light dawned. We got the curve by the tail...mister. You'd better hang on! ~ les